Prenatal alcohol exposure can produce Fetal Alcohol Syndrome (FAS) and Alcohol-Related Neurodevelopmental Delays (ARNDs) which are associated with cognitive disabilities and mental retardation. To date, there are no specific treatments for these fetal alcohol effects. In recent years, we examined the ability of postnatal environmental manipulations to ameliorate fetal alcohol effects on brain and behavior. We demonstrated that rearing rats in an enriched environment, with increased opportunities for sensory stimulation, motor activity and social interactions, reduced the behavioral impact of prenatal alcohol exposure in a rodent model of ARNDs. We also demonstrated that in rats exposed prenatally to alcohol, enrichment did not induce normal neuronal plasticity (i.e., increases in dendritic spine densities) in hippocampus, a brain area particularly sensitive to prenatal alcohol., The proposed studies will extend these findings by determining the age(s) at which optimal effects of environmental enrichment occur and by assessing the permanence of enrichment effects on behavior. The proposed research will examine several dose-dependent morphological and neurotrophic outcomes in neocortex (visual and prefrontal), and in hippocampus, to assess why hippocampus in alcohol-exposed offspring was not responsive to enrichment and what brain areas may mediate behavioral amelioration. The effects of parental alcohol and environment enrichment on mRNA and protein levels of specific immediate early genes (IEGs) neurotrophic factors (i.e., Nerve Growth Factor, Neurotrophin-3, Growth Associated Protein-43) important for brain growth, development and plasticity will be measured. We will study mechanisms of neuroplastic dysfunction including measures of IEG activation in response to environmental stimulation. The experiments represent an integrated multi-disciplinary study of the effects of selected patterns of environmental enrichment (e.g., age and onset) and gender on dose-dependent prenatal alcohol effects on neuroanatomy, neurochemistry and behavior. The results will help answer questions about how prenatal alcohol-induced damage to the CNS can be ameliorated postnatally. The results could have direct implications for the development of effective and appropriate treatments for FAS/ARNDs in children.